key: cord-0891244-zxkohvme
authors: Nanthatanti, Nithita; Phusanti, Sithakom; Chantrathammachart, Pichika; Thammavaranucupt, Kanin; Angchaisuksiri, Pantep; Sungkanuparph, Somnuek
title: Left ventricular thrombus and pulmonary embolism: A case series of thrombosis in COVID‐19 in Thai patients
date: 2020-10-13
journal: Res Pract Thromb Haemost
DOI: 10.1002/rth2.12435
sha: bae1f8a6f86015d98a886f9fb68e91a8a101dc14
doc_id: 891244
cord_uid: zxkohvme

Thrombosis in COVID‐19 is increasingly recognized and is generally associated with a high mortality rate. The key clinical question of this report was whether COVID‐19 could be complicated with cardiac thrombus and pulmonary embolism in Asian population. We demonstrated the case series of thrombosis in Thai patients with confirmed severe acute respiratory syndrome coronavirus 2 infection. One patient had the first case of a large left ventricular thrombus, and three other patients had pulmonary embolism. All patients were male and had low absolute lymphocyte count, while lactate dehydrogenase level and d‐dimer were markedly elevated, especially at the time when the thrombosis was diagnosed. All patients had severe COVID‐19 with pneumonia. Two patients who needed mechanical ventilation were successfully extubated. After hospitalization for 13‐49 days, pneumonia and thrombosis improved and all of them could be discharged from the hospital. Thrombosis is common in COVID‐19 and could present in both arterial and venous sites even in Asian populations. d‐dimer is a strong marker to predict thrombosis and could be a prognostic predictor for severity of COVID‐19.

There is a high prevalence of venous thromboembolism (VTE) among patients with severe coronavirus disease 2019 (COVID- 19) . 1 According to recent studies, the incidence of pulmonary embolism (PE) in patients with COVID-19 pneumonia in the intensive care unit (ICU) ranged from 22% to 69%. [2] [3] [4] [5] However, thrombosis in Thai patients with COVID-19 has not been reported. Some reports have shown that thrombosis in COVID-19 could present in various sites-for instance, pulmonary, mesenteric, and intracranial vessels-and was associated with a high mortality rate. 4, 6 A lower incidence of VTE was reported in the Asian population than in the White population. 7 The key clinical question of this report was whether COVID-19 could be complicated with cardiac thrombus and PE in Asian populations. Here, we report a case series of patients with severe COVID-19 pneumonia who developed thrombosis in our cohort of 144 patients admitted in our hospital. 8 We defined severe COVID- 19 according to the World Health Organization definition (fever or suspected respiratory infection plus one of the following: respiratory rate >30/min or oxygen saturation ≤93% on room air). 9 All of them survived. We would like to raise awareness that PE also occurs in Asian patients with COVID-19 and pharmacological thromboprophylaxis is essential in Asian patients hospitalized with COVID-19.

A 71-year-old man presented with acute watery diarrhea for 10 days and was found to have COVID-19. His underlying health risks were hypertension, dyslipidemia, and a history of coronary artery disease (CAD) with balloon angioplasty for 10 years. He had taken clopidogrel and an angiotensin-converting enzyme inhibitor daily for secondary prevention of CAD. His vital signs at admission were normal and oxygen saturation was 95% on room air. Baseline chest radiograph revealed ground-glass opacities at both lower lung fields. His complete blood count showed a low absolute lymphocyte count (ALC) of 1020/mm 3 , elevated lactate dehydrogenase (LDH) level of 317 U/L (135-225) and high d-dimer of 1548 ng/mL fibrinogen equivalent units (FEU). He was treated with hydroxychloroquine and darunavir/ ritonavir on the first day of admission (the 10th day of his illness).

On the 11th day of illness, the patient's symptoms progressed and oxygen saturation decreased to 93% on room air as a result of severe pneumonia. His symptoms and oxygen saturation improved after a complete course of favipiravir and supportive oxygen therapy. Due to the extremely high level of d-dimer (40 560 ng/mL FEU) on 19th day of illness (Table 1) , PE was suspected, and computed tomography pulmonary angiography (CTPA) was performed. PE was not detected. However, a large 4.1 × 2.0 cm. thrombus was seen in the left ventricle ( Figure 1A ). Echocardiogram confirmed a large LV 

A 44-year-old man presented with fever for 7 days and was diagnosed Figure 1D ). Therapeutic On the 30th day of illness, tension hemothorax was detected, and a percutaneous drainage tube was inserted. VV-ECMO was later removed, and UFH was changed to LMWH. Finally, he was extubated on the 39th day of illness and discharged on the 54th day of his illness with warfarin.

A Laboratory results showed markedly elevated d-dimer levels (15 320 ng/mL FEU), low ALC, and elevated LDH and interleukin-6.

He was treated with therapeutic LMWH. Eventually, he was extubated on the 28th day of illness and discharged on the 42nd day of his illness with warfarin.

A 44-year-old guitarist presented with fever and progressive dyspnea for 12 days and was confirmed to have COVID-19. He had a history of hypertension and dyslipidemia. Chest radiograph demonstrated bilateral ground-glass opacities of both lower lung zones. He received hydroxychloroquine, darunavir/ritonavir, azithromycin, and favipiravir for COVID-19 pneumonia.

On the 14th day of illness, the patient developed impending respiratory failure. During that period, his d-dimer level was extremely high (67 820 ng/mL FEU). (Table 1 ) CTPA revealed acute PE involving bilateral lobar and segmental pulmonary arteries ( Figure 1F ). Therapeutic doses of LMWH were given. His condition improved, and he was discharged home with warfarin on the 29th day of illness.

We have demonstrated four cases of thrombosis in Thai patients with severe COVID-19, one case with a large thrombus in the left ventricle and three cases with PE. All patients had severe pneumonia and received the same regimen of antiviral agents. All were males and were characterized by having baseline lymphopenia with markedly elevated d-dimer levels. Table 1 All patients had severe pneumonia and received the same regimen of antiviral agents. Three patients who had PEs were admitted to the ICU. Recent study has shown that critically ill patients with COVID-19 were at a higher risk for the development of a PE than patients with influenza. 3 Global data have also shown that disease severity and mortality from COVID-19 are higher among men than women. Multiple dimensions of biological sex, including sex steroids, sex chromosomes, and genomic and epigenetic differences between men and women impact immune responses and may affect responses to SARS-CoV-2 infection. In addition, underlying preexisting comorbidities (such as ischemic heart disease, diabetes, or hypertension) and high-risk behaviors (such as smoking and alcohol use) are more frequent in men. Sex differences in angiotensin-converting enzyme 2 (ACE2) receptors and ACE2 enzyme activity have also been proposed. 10, 11 We have demonstrated the first case report of a large LV thrombus in a patient with COVID-19 pneumonia (case 1). There are several known conditions associated with cardiac thrombi such as atrial fibrillation or ischemic cardiomyopathy. 12 However, the exact cause of thrombus in the left ventricle in this patient was unknown.

Cardiac thrombi in ischemic cardiomyopathy usually develops in patients with severely impaired left ventricular ejection fraction. 12, 13 Our patient only had mildly impaired cardiac function and did not 4 There were also reported cases of aortic thrombi. 15, 16 The mechanism of the hypercoagulability leading to arterial

thrombosis is yet to be fully elucidated. The proposed mechanism of SARS-CoV-2 internalization into human host cells assumes that the viral particles bind to ACE2 receptors, which abundantly present at multiple tissues, especially lung and endothelial cells. SARS-CoV-2 infection can produce endothelial dysfunction due to direct inva- bus is a rare complication of stress cardiomyopathy. Although the specific mechanism of ventricular thrombus in COVID-19 is not fully understood, it could be due to hypercoagulability and local myocardial inflammation creating an area of relatively static blood that is prone to thrombus formation.

d-dimer has been proposed as a prognostic marker of disease severity and mortality in patients with COVID-19. 18, 19 Although d-dimer level can rise in many conditions, it is considered a sensitive indicator for identifying the risk of VTE. 2, 4, 20 One study from China suggested that the acceptable cutoff value of d-dimer levels to predict VTE was 1500 ng/mL FEU with the sensitivity and specificity of 85% and 88.5%, respectively. 20 One study from China demonstrated that the prevalence of VTE was 25% in patients who did not receive anticoagulant prophylaxis. 20 All had a lower extremity venous thrombosis. PE was not reported. Studies from Europe revealed that 20%-69% of patients with COVID-19 experienced breakthrough symptomatic VTE even on prophylactic thromboprophylaxis. [2] [3] [4] [5] The optimal dose of LMWH thromboprophylaxis is controversial. A higher dose of LMWH may be required for preventing VTE in this situation. [2] [3] [4] [5] 21 Several randomized controlled trials looking at the appropriate intensity of LMWH prophylaxis are still ongoing in patients with COVID-19.

In conclusion, this report addresses the problem of thrombosis in COVID-19 in the Asian population. Awareness of thrombosis and prompt diagnosis and treatment are crucial in COVID-19 patients.

Moreover, this report supports the recommendation that thromboprophylaxis is required in Asian patients with severe COVID-19 pneumonia.

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How to cite this article

Left ventricular thrombus and pulmonary embolism: A case series of thrombosis in COVID-19 in Thai patients

The authors report nothing to disclose. Somnuek Sungkanuparph https://orcid.org/0000-0002-1055-2963

Somnuek Sungkanuparph @S_Sungkanuparph